Funds are requested for the replacement of old NMR consoles for cryoprobe-equipped 600 MHz and 800 MHz NMR spectrometers located in the Vanderbilt University Center for Structural Biology (VCSB) with state-of-the-art consoles. The current Bruker DRX consoles for the solution NMR spectrometers of the VCSB are now 8 years old and are technically out of date and beginning to break down on a frequent basis. Funds are requested that will be pooled with institutional commitments to replace the 2 most critical of the aging consoles with Bruker Avance III consoles. In addition to enhancing the reliability of the NMR equipment, the new consoles and their integrated software are expected to perform at a much higher level than the current out-of-date systems and also to have expanded technical capabilities. The instrumentation for which the new consoles are sought is overseen on a daily basis by a dedicated NMR facilities manager, Dr. Markus Voehler, an accomplished NMR spectroscopist with over 20 years of experience working on biomolecular systems. The new consoles are critical to the success of the NIH-funded biomolecular research of both a group of four major users (C. Sanders, W. Chazin, M. P. Stone, A. Krezel), all of whom are experts in biomolecular NMR, and of minor users (represented in this application by B. Eichman, B. Hudson, and J. Meiler). Included in the work of the user groups are studies that are extremely demanding from an NMR standpoint, including solution NMR studies of integral membrane proteins, large soluble proteins and protein-protein complexes that have aggregate molecular weights in the range of 100 kD. A number of the projects involve biomolecular problems of direct relevance to human disease. PUBLIC HEALTH RELEVANCE: Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique that is used to study the three-dimensional structures, motions, and interactions of biological molecules. NMR is used by a number of NIH-supported investigators at Vanderbilt University to study biomolecules that are of both direct and indirect relevance to human health and disease. The application requests the funds required to replace out-of-date and increasingly-unreliable NMR equipment with fully state-of-the-art equipment, as is critical to the continuing success of the biological and biomedical research programs of the investigators associated with this application and a growing community of additional users who are just realizing the power of NMR.